Bioactive constituents of Melia volkensii Gurke (Meliaceae)
Abstract
During our broad screening for bioactive plants, the extracts of the root bark of Melia volkensii Gurke (Meliaceae) showed potent activity in the brine shrimp lethality test (BST). Plants in the family of Meliaceae are usually characterized by the presence of a group of secondary metabolites known as limonoids. Information obtained so far has shown a wide range of biological activities for these compounds, including insect antifeedant and growth regulating properties, a variety of medicinal effects in animals and humans, as well as antifungal, antibactericidal and antiviral effects. The objective of this project is to find the bioactive components in the root bark of M. volkensii, a subtropical tree widely distributed in the dry areas of east Africa. Bioactivity directed fractionation has resulted in the isolation of eight (1-8) limonoids and four steroids (9-12). Four of the limonoids (2, 3, 5, and 7) and the four steroids are new to the literature; three of the known limonoids (1, 4, 8) were isolated for the first time from this species, and compound 6 had been isolated previously from the fruit of the same species. The planar structures of the novel compounds isolated were determined by spectral analysis, including IR; UV; low and high resolution CIMS, EIMS, and FABMS; 1D ($\sp1$H and $\sp{13}$C) and 2D-NMR (COSY, relay-COSY, HMQC, and HMBC) experiments; as well as by chemical derivatizations. The relative stereochemistries of the structures were established by NOESY experiments, and the absolute configurations of the carbinol centers in compound 4 were established by Mosher ester methods. All of the isolated compounds and some of their derivatives have been tested for in vitro antitumor activities in a panel of six human tumor cell lines. Compound 8 showed general cytotoxicities stronger than those of the positive control compound, adriamycin, in all the six cell lines, compounds 4d, 6, 7, and 10 showed not only significant but also selective ED$\sb{50}$ values, and the others showed moderate to weak activities.
Degree
Ph.D.
Advisors
McLaughlin, Purdue University.
Subject Area
Pharmacology|Analytical chemistry
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